Clinical and translational research on cancer of the stomach and gastroesophageal junction: A pathologist's view

Adenocarcinomas of the stomach and gastroesophageal junction remain one of the most common malignant tumours in humans worldwide, often with a poor prognosis. Particularly in countries without upper gastrointestinal tract screening endoscopy, tumours that have been asymptomatic for a long time are only diagnosed at an advanced stage. This limits the therapeutic options. Often only palliative therapy concepts are available. Great progress has been made in the last two decades. The genetic basis of adenocarcinomas of the stomach and gastroesophageal junction has been deciphered and new targeted drugs have been developed. Cell and tissue-based predictive diagnostics are becoming increasingly important in therapy planning. Here, surgical pathology forms an important link between basic research, clinical trials, and translation into clinical application. This review article summarizes the experiences made in translational tumour research, which point to the problems of spatial and temporal intratumoral heterogeneity of adenocarcinomas of the stomach and gastroesophageal, the development and continuous re-assessment of therapeutically relevant cut-off values, resistance mechanisms, tumour microenvironment, sexual dimorphism and the pitfalls molecular tumour boards may face. (A) Adenocarcinoma of the stomach and gastroesophageal junction is a heterogeneous disease with considerable interindividual genetic and phenotypic differences, which influence prognosis and therapeutic success.(B) Treatment options and the associated use of predictive biomarkers are increasing.(C) Spatial and temporal intratumoral heterogeneity represents the greatest risk in personalized medicine for these tumours.(D) Surgical pathologists are central in guiding oncological patient management and translational studies. image